The goal of this research is to develop and validate a method using Laser Speckle Imaging to measure the intrinsic biomechanical properties of atherosclerotic plaques. The rupture of unstable atherosclerotic plaque, the most frequent event leading to thrombus mediated ischemic cardiovascular disease, is caused when the mechanical stability of the atheroma is compromised. Techniques that evaluate the mechanical properties of atherosclerotic plaques are vital for identifying rupture-prone atherosclerotic plaques, guiding therapy, and for providing insights regarding plaque stabilization in patients. We recently showed that Laser Speckle Imaging (LSI), a new optical technique which measures the Brownian motion of endogenous particles in tissue, is highly sensitive for evaluating plaque viscoelasticity, composition and structure. Our prior work, conducted on cadaveric arterial specimens demonstrated that LSI has high accuracy for diagnosing atherosclerotic plaque type, measuring collagen content, and necrotic core area, and determining fibrous cap thickness. The goal of the current proposal is to develop a method which measures the time scale and mean square displacement of endogenous particles to calculate accurately evaluate vessel viscoelastic properties. The Aims of this proposal are motivated by our prior experience in investigating the diagnostic potential of LSI. Subsequently, we will use this method to monitor vessel mechanical properties in a mouse model of atherosclerosis. Viscoelastic properties of the vessel will be monitored over time during plaque progression and at sacrifice these results will be correlated to histological findings. The methods developed in this work present the potential for measuring the biomechanical properties of atherosclerotic plaques in vivo to detect rupture prone plaques and may facilitate the development of improved therapeutic approaches. Narrative: This work will present a significant contribution in determining the influence of arterial viscoelasticity on the pathogenesis of plaque rupture. Completion of this work will result in the determination of a key biomechanical marker associated with plaque instability and will move us towards the eventual goal of identifying high-risk plaques in patients.